A Modified Continual Reassessment Method for Balancing Individual- and Population-Ethics in Phase I Clinical Trials

• Activity Number: 337
• Type: Invited
• Date/Time: Tuesday, August 11, 2015 : 10:30 AM to 12:20 PM
• Sponsor: WNAR
• Author(s): Daniel Gillen* and Steven Kim
• Companies: UC Irvine and UC Irvine
• Keywords: Dose finding ; Bayesian ; Continual Reassessment ; Ethics ; Clinical trials

Abstract

The typical objective of a Phase I clinical trial is to study the toxicity of a treatment and to determine a maximum tolerable dose (MTD) for future patients. O'Quigley, Pepe and Fisher (1990) proposed the continual reassessment method (CRM), a Bayesian adaptive design, to overcome many of the ethical and statistical concerns confronted in dose finding studies where limited data are available. The CRM seeks to treat newly enrolled patients at the posterior mean of the dose corresponding to a pre-specified risk level. Taking a different perspective from the CRM, Whitehead and Brunier (1995) applied Bayesian decision theory to phase I clinical trials wherein the gain function was defined as the inverse of the asymptotic variance of the maximum likelihood estimator for the MTD. The objective of this strategy was hence to optimize dose allocation to maximize the precision of the resulting MTD estimate at the conclusion of the trial. As such, the information gain method of Whitehead and Brunier can be viewed as an allocation procedure concerned with treating future patients (outside of the current trial) by focusing on precision, while the CRM approach can be viewed as an allocation pr